Back to results

AMG 176 With Azacitidine in Subjects With Myelodysplastic Syndrome /Chronic Myelomonocytic Leukemia

Primary Purpose

Higher Risk Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

AMG 176

Azacitidine

About this trial

This is an interventional treatment trial for Higher Risk Myelodysplastic Syndrome focused on measuring Higher Risk Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndrome, Myelomonocytic Leukemia

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age >= 18 years of age
For Part 1, participants have R/R MDS post-HMA failure, defined as prior receipt of 4 cycles of HMA therapy (including but not limited to decitabine, azacitidine, investigational HMAs such as SGI-110, and oral HMAs such as oral decitabine and cedazuridine [ASTX727] and oral azacitidine [CC-486]) with failure to attain a response or progression of disease or relapse at any time after prior response to HMA therapy
a. Note: participants with HR-CMML (CMML-1 or 2 by World Health Organization [WHO]) are eligible. Hydroxyurea administration will be allowed on the study to lower the white cell count to <= 10 000/μL prior to the initiation of therapy
For Part 2, participants will be divided into 2 cohorts:
1. HMA Failure Cohort: participants with R/R MDS post-HMA failure. Participants who have previously received venetoclax are eligible and will be stratified accordingly in the HMA failure cohort;
2. Newly Diagnosed Cohort: Participants with treatment-naïve newly diagnosed HR-MDS (revised International Prognostic Scoring System [IPSS-R] score >3.5) are eligible for enrollment only after all prior cohorts have been completed. Hydroxyurea administration will be allowed on the study to lower the white cell count to <= 10 000/μL prior to the initiation of therapy. Participants with HR-CMML (CMML-1 or 2 by WHO) are eligible

Exclusion Criteria:

Participants with newly diagnosed MDS with Revised International Prognostic Scoring System (IPSS-R) lower-risk category (IPSS-R score < 3.5)
Participants with CMML-0 by WHO
History of other malignancy within the past 2 years prior to enrollment (with some exceptions as listed in full list of criteria)
Excluded prior and/or concomitant therapies as listed in the full list of criteria
Participants who are fit and deemed eligible by the investigator for intensive salvage therapy

Sites / Locations

University of Texas MD Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Part 1A - AMG 176 Monotherapy (Dose Exploration)

Part 1B - AMG 176 and Azacitidine Combination Therapy (Dose Exploration)

Part 2 - AMG 176 and Azacitidine Combination Therapy (Dose Expansion)

Arm Description

Two dose levels of AMG 176 will be tested in Part 1A to find the optimal biological dose/minimum safe biologically effective dose (OBD/MSBED).

After the OBD is found in Part 1A, two dose levels of AMG 176 in combination with azacitidine will be tested in Part 1B to find the OBD/MSBED.

After the completion of Part 1, the Part 2 dose expansion phase will begin at the OBD/MSBED identified in Part 1. Venetoclax-naïve and venetoclax-exposed R/R HR-MDS participants after HMA failure will be enrolled along with participants with newly diagnosed HR-MDS/CMML.

Outcomes

Primary Outcome Measures

Part 1A and 1B: Number of Participants Who Experience a Dose Limiting Toxicity (DLT)

Part 1A and 1B: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)

Part 2: Overall Response Rate (ORR)

As assessed according to the Uniform Response Criteria for Myelodysplastic/ Myeloproliferative Neoplasms (MDS/MPN).

Secondary Outcome Measures

Part 1A and Part 1B: Overall Response

As assessed according to the Uniform Response Criteria for MDS/MPN for R/R MDS/CMML participants.

Part 1A, Part 1B and Part 2: Event-free Survival (EFS)

Part 1A and Part 1B: Time to Response (TTR)

Part 1A, Part 1B and Part 2: Duration of Response (DoR)

Part 1A: Maximum Concentration (Cmax) of AMG 176 when Administered as Monotherapy

Part 1A: Area Under the Concentration-time Curve (AUC) of AMG 176 when Administered as Monotherapy

Part 1A: Clearance (CL) of AMG 176 when Administered as Monotherapy

Part 1A: Half-life (t1/2) of AMG 176 when Administered as Monotherapy

Part 1B and Part 2: Cmax of AMG 176 when Administered in Combination

Part 1B and Part 2: AUC of AMG 176 when Administered in Combination

Part 1B and Part 2: CL of AMG 176 when Administered in Combination

Part 1B and Part 2: T1/2 of AMG 176 when Administered in Combination

Part 1B and Part 2: Cmax of Azacitidine when Administered in Combination

Part 1B and Part 2: AUC of Azacitidine when Administered in Combination

Part 1B and Part 2: CL of Azacitidine when Administered in Combination

Part 1B and Part 2: T1/2 of Azacitidine when Administered in Combination

Part 2: Time to Transformation to Acute Myeloid Leukemia (AML)

Part 2: Overall Survival (OS)

Part 2: Time to Next MDS Treatment (TTNT)

Full Information

NCT ID

NCT05209152

First Posted

January 13, 2022

Last Updated

October 20, 2023

Sponsor

Amgen

1. Study Identification

Unique Protocol Identification Number

NCT05209152

Brief Title

AMG 176 With Azacitidine in Subjects With Myelodysplastic Syndrome /Chronic Myelomonocytic Leukemia

Official Title

A Phase 1 Study of AMG 176 as Monotherapy and in Combination With Azacitidine in Higher-Risk Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 14, 2022 (Actual)

Primary Completion Date

December 12, 2025 (Anticipated)

Study Completion Date

December 13, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Amgen

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

The main objective is to assess the safety, tolerability, and efficacy of AMG 176 as monotherapy and in combination with the 7-day regimen of azacitidine for the treatment of Higher-Risk Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia (HR-MDS/CMML).

Detailed Description

This study is a Phase 1 clinical trial designed to assess the safety, tolerability, and efficacy of AMG 176 as monotherapy and in combination with the 7-day regimen of azacitidine for the treatment of HR-MDS/CMML. Participants will be treated with intravenous (IV) AMG 176 and IV or subcutaneous (SC) azacitidine.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Higher Risk Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia

Keywords

Higher Risk Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndrome, Myelomonocytic Leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Part 1A - AMG 176 Monotherapy (Dose Exploration)

Arm Type

Experimental

Arm Description

Two dose levels of AMG 176 will be tested in Part 1A to find the optimal biological dose/minimum safe biologically effective dose (OBD/MSBED).

Arm Title

Part 1B - AMG 176 and Azacitidine Combination Therapy (Dose Exploration)

Arm Type

Experimental

Arm Description

After the OBD is found in Part 1A, two dose levels of AMG 176 in combination with azacitidine will be tested in Part 1B to find the OBD/MSBED.

Arm Title

Part 2 - AMG 176 and Azacitidine Combination Therapy (Dose Expansion)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

AMG 176

Intervention Description

Administered as an intravenous (IV) infusion.

Intervention Type

Drug

Intervention Name(s)

Azacitidine

Intervention Description

Administered as an IV infusion or subcutaneous (SC) injection.

Primary Outcome Measure Information:

Title

Part 1A and 1B: Number of Participants Who Experience a Dose Limiting Toxicity (DLT)

Time Frame

Day 1 to Day 28

Title

Part 1A and 1B: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)

Time Frame

Up to 1.5 years

Title

Part 2: Overall Response Rate (ORR)

Description

As assessed according to the Uniform Response Criteria for Myelodysplastic/ Myeloproliferative Neoplasms (MDS/MPN).

Time Frame

Up to 1.5 years

Secondary Outcome Measure Information:

Title

Part 1A and Part 1B: Overall Response

Description

As assessed according to the Uniform Response Criteria for MDS/MPN for R/R MDS/CMML participants.

Time Frame

Up to 1.5 years

Title

Part 1A, Part 1B and Part 2: Event-free Survival (EFS)

Time Frame

Up to 1.5 years

Title

Part 1A and Part 1B: Time to Response (TTR)

Time Frame

Up to 1.5 years

Title

Part 1A, Part 1B and Part 2: Duration of Response (DoR)

Time Frame

Up to 1.5 years

Title

Part 1A: Maximum Concentration (Cmax) of AMG 176 when Administered as Monotherapy

Time Frame

Cycle 1 (=23 days) Day 1 and Day 8: Pre-dose and 0.5, 3, 5, 7, 8, 12 (Day 8 only) and 24 hours post-dose. Day 15 and 22: Pre-dose and 0.5, 8 and 24 hours post-dose. Cycle 2-4 (=23 days) Day 1: Pre-dose and 0.5 and 24 hours post-dose

Title

Part 1A: Area Under the Concentration-time Curve (AUC) of AMG 176 when Administered as Monotherapy

Time Frame

Title

Part 1A: Clearance (CL) of AMG 176 when Administered as Monotherapy

Time Frame

Title

Part 1A: Half-life (t1/2) of AMG 176 when Administered as Monotherapy

Time Frame

Title

Part 1B and Part 2: Cmax of AMG 176 when Administered in Combination

Time Frame

Title

Part 1B and Part 2: AUC of AMG 176 when Administered in Combination

Time Frame

Title

Part 1B and Part 2: CL of AMG 176 when Administered in Combination

Time Frame

Title

Part 1B and Part 2: T1/2 of AMG 176 when Administered in Combination

Time Frame

Title

Part 1B and Part 2: Cmax of Azacitidine when Administered in Combination

Time Frame

Cycle 1 (=23 days) Day 1: Pre-dose, 5 mins post-dose, 30 mins post-dose, 1, 2, 4, and 8 hours post-dose.

Title

Part 1B and Part 2: AUC of Azacitidine when Administered in Combination

Time Frame

Cycle 1 (=23 days) Day 1: Pre-dose, 5 mins post-dose, 30 mins post-dose, 1, 2, 4, and 8 hours post-dose.

Title

Part 1B and Part 2: CL of Azacitidine when Administered in Combination

Time Frame

Cycle 1 (=23 days) Day 1: Pre-dose, 5 mins post-dose, 30 mins post-dose, 1, 2, 4, and 8 hours post-dose.

Title

Part 1B and Part 2: T1/2 of Azacitidine when Administered in Combination

Time Frame

Cycle 1 (=23 days) Day 1: Pre-dose, 5 mins post-dose, 30 mins post-dose, 1, 2, 4, and 8 hours post-dose.

Title

Part 2: Time to Transformation to Acute Myeloid Leukemia (AML)

Time Frame

Up to 1.5 years

Title

Part 2: Overall Survival (OS)

Time Frame

Up to 1.5 years

Title

Part 2: Time to Next MDS Treatment (TTNT)

Time Frame

Up to 1.5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age >= 18 years of age For Part 1, participants have R/R MDS post-HMA failure, defined as prior receipt of 4 cycles of HMA therapy (including but not limited to decitabine, azacitidine, investigational HMAs such as SGI-110, and oral HMAs such as oral decitabine and cedazuridine [ASTX727] and oral azacitidine [CC-486]) with failure to attain a response or progression of disease or relapse at any time after prior response to HMA therapy a. Note: participants with HR-CMML (CMML-1 or 2 by World Health Organization [WHO]) are eligible. Hydroxyurea administration will be allowed on the study to lower the white cell count to <= 10 000/μL prior to the initiation of therapy For Part 2, participants will be divided into 2 cohorts: HMA Failure Cohort: participants with R/R MDS post-HMA failure. Participants who have previously received venetoclax are eligible and will be stratified accordingly in the HMA failure cohort; Newly Diagnosed Cohort: Participants with treatment-naïve newly diagnosed HR-MDS (revised International Prognostic Scoring System [IPSS-R] score >3.5) are eligible for enrollment only after all prior cohorts have been completed. Hydroxyurea administration will be allowed on the study to lower the white cell count to <= 10 000/μL prior to the initiation of therapy. Participants with HR-CMML (CMML-1 or 2 by WHO) are eligible Exclusion Criteria: Participants with newly diagnosed MDS with Revised International Prognostic Scoring System (IPSS-R) lower-risk category (IPSS-R score < 3.5) Participants with CMML-0 by WHO History of other malignancy within the past 2 years prior to enrollment (with some exceptions as listed in full list of criteria) Excluded prior and/or concomitant therapies as listed in the full list of criteria Participants who are fit and deemed eligible by the investigator for intensive salvage therapy

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Amgen Call Center

Phone

866-572-6436

medinfo@amgen.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Organizational Affiliation

Amgen

Official's Role

Study Director

Facility Information:

Facility Name

University of Texas MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

IPD Sharing Time Frame

Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.

IPD Sharing Access Criteria

Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

IPD Sharing URL

https://www.amgen.com/datasharing

Links:

URL

http://www.amgentrials.com

Description

AmgenTrials clinical trials website

Learn more about this trial

AMG 176 With Azacitidine in Subjects With Myelodysplastic Syndrome /Chronic Myelomonocytic Leukemia

We'll reach out to this number within 24 hrs